Current treatments for human immunodeficiency virus (HIV) include inhibitors of HIV proteases; but these inhibitors can have severe side effects. Also, there has been a rapid emergence of HIV strains that are drug resistant, e.g., insensitive to currently used HIV inhibitors, including HIV protease inhibitors.
HIV-1 protease (PR), an aspartyl protease, is required for the efficient processing of the Gag and Gag-Pol precursor polyproteins; a critical step in the viral life cycle. For this reason, targeting PR has long been the focus of anti-retroviral therapy. However, aside from its proteolytic activity, its effects on the host cell are still unclear. Cytotoxic effects, together with instability, render expression of PR in mammalian cells difficult. Elucidating the role of PR in the viral life cycle, as well as discerning its effects on the host machinery, is vital for the design of novel therapeutic approaches.